New estrogens in the pipeline
Neither of these developments, however, have eliminated the risks associated with hormone therapy for women of older age or for women at high risk for breast cancer. Although total elimination of risk may not be possible, recent research suggests that the naturally occurring fetal estrogens estriol and estetrol appear to have SERM-like properties, Dr. Taylor said. These estrogens are made only in pregnancy and appear to have evolved for a purpose different from that of estrone and estradiol.
“While both are weak estrogens by traditional standards, both have unique properties that make them very interesting for therapeutic use,” Dr. Taylor said. In particular, estetrol has a much longer half-life than estriol, making it more appropriate for therapeutic investigation.
A study of estetrol that was published in Menopause in August 2020 showed encouraging results. Despite a fairly sizable placebo effect, there was also a dose-response effect from estetrol on vasomotor symptoms. Low doses did not have much effect, but with higher doses (15 mg), there was a robust, significant improvement in the frequency and severity of hot flashes. So far, Dr. Taylor said, it looks like estetrol can be a highly effective treatment for vasomotor symptoms.
In addition, preclinical research suggests that estetrol may have a better safety profile than currently available therapies, though much more work is needed to know for sure. For example, a 2015 study found that it requires extremely high doses – well above therapeutic levels – for tumor growth to occur. Similarly, a 2019 study found that very high doses of estetrol or estriol were needed before it would stimulate breast cancer cell growth, likely because these are such weak estrogens, compared with estradiol, Dr. Taylor said.
There is currently less information on estetrol’s potential cardiovascular effects, but an animal model suggests positive effects, he said. Giving a mouse estetrol led to an increase in blood vessel dilation with increased blood flow.
The reason these estrogens appear to pose less risk yet still show therapeutic effects appears related to how they bind to the estrogen receptor and what their purpose is, Dr. Taylor told attendees.
“These fetal estrogens are really there probably for developmental programming,” he said. “It’s no wonder they may have some unique and favorable properties for therapeutic use. I’m really enthusiastic to see this explored further as a potential new hormonal therapy.”
Dr. Taylor disclosed no relevant financial relationships. Dr. Santoro reported stock ownership in Menogenix and consulting or advising for Ansh Labs, Menogenix, and Ogeda/Astellas.
A version of this article originally appeared on Medscape.com.